Brain Metastases

VERSION: 1.0 CREATED: January 27, 2026 STATUS: Approved

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DIAGNOSIS: Brain Metastases

ICD-10: C79.31 (Secondary malignant neoplasm of brain), C79.32 (Secondary malignant neoplasm of cerebral meninges), C79.49 (Secondary malignant neoplasm of other parts of nervous system), G93.6 (Cerebral edema due to neoplasm)

CPT CODES: 85025 (CBC with differential), 80053 (CMP (BMP + LFTs)), 82947 (Blood glucose), 84484 (Troponin), 84703 (Pregnancy test (β-hCG)), 83615 (LDH), 87389 (HIV, hepatitis B/C), 82533 (Cortisol (AM)), 88104 (CSF cytology / flow cytometry), 70450 (CT head without contrast), 70553 (MRI brain with and without contrast (gadolinium)), 93000 (ECG (12-lead)), 71046 (Chest X-ray), 78816 (PET/CT (FDG)), 70496 (CT angiography (head)), 62270 (LP), 96374 (Dexamethasone (vasogenic edema))

SYNONYMS: Brain metastases, brain mets, cerebral metastases, brain metastasis, metastatic brain tumor, secondary brain tumor, secondary brain cancer, metastatic brain disease, brain tumor from cancer, metastatic disease to brain, brain lesions, CNS metastases

SCOPE: Management of newly diagnosed or progressive brain metastases in adults. Covers initial stabilization, vasogenic edema management with corticosteroids, seizure management, imaging evaluation, molecular/histopathologic workup, treatment modalities (surgery, stereotactic radiosurgery, whole-brain radiation, systemic therapy with CNS penetration), and disposition. Excludes primary brain tumors (separate template), leptomeningeal carcinomatosis (partially addressed), and spinal metastases (separate template).

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PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════

1. LABORATORY WORKUP

1A. Essential/Core Labs

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
CBC with differential (CPT 85025)	STAT	STAT	ROUTINE	STAT	Baseline; chemotherapy planning; leukocytosis/infection; thrombocytopenia (bleeding risk, treatment candidacy)	WBC, platelets within normal limits; ALC (absolute lymphocyte count) for immunotherapy eligibility
CMP (BMP + LFTs) (CPT 80053)	STAT	STAT	ROUTINE	STAT	Renal function for contrast imaging; hepatic function for chemotherapy dosing; electrolytes (SIADH from brain lesions); glucose (steroid hyperglycemia)	Normal; anticipate glucose elevation with dexamethasone
PT/INR, aPTT (CPT 85610+85730)	STAT	STAT	ROUTINE	STAT	Coagulopathy assessment; surgical candidacy; hemorrhagic metastases (melanoma, RCC, choriocarcinoma, thyroid)	Normal
Blood glucose (CPT 82947)	STAT	STAT	ROUTINE	STAT	Steroid-induced hyperglycemia; baseline before dexamethasone	<180 mg/dL; start insulin if persistently elevated
Troponin (CPT 84484)	STAT	STAT	-	STAT	Cardiac evaluation if syncope or neurogenic cardiac injury	Normal
Pregnancy test (β-hCG) (CPT 84703)	STAT	STAT	ROUTINE	STAT	Treatment planning; β-hCG-secreting tumors (choriocarcinoma, germ cell); radiation contraindication in pregnancy	Negative; if elevated consider choriocarcinoma or germ cell tumor
LDH (CPT 83615)	STAT	ROUTINE	ROUTINE	STAT	Melanoma staging; tumor burden marker; prognostic	Normal; elevated in melanoma, lymphoma
TSH, free T4 (CPT 84443+84439)	-	ROUTINE	ROUTINE	-	Thyroid primary (thyroid cancer with brain metastases); fatigue/cognitive symptoms differential	Normal; abnormal may indicate thyroid primary

1B. Extended Workup (Second-line)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Tumor markers (CEA, CA 19-9, CA 125, CA 15-3, AFP, β-hCG) (CPT 82378, 86301, 86304, 82105, 84703)	-	ROUTINE	ROUTINE	-	Unknown primary: CEA (lung, GI, breast), CA 19-9 (pancreatic, GI), CA 125 (ovarian), CA 15-3 (breast), AFP (hepatocellular, germ cell), β-hCG (choriocarcinoma, germ cell)	Elevations guide primary site evaluation
PSA (males)	-	ROUTINE	ROUTINE	-	Prostate cancer with brain metastases (rare but occurs)	Normal; elevated guides prostate workup
Serum protein electrophoresis (SPEP)	-	ROUTINE	ROUTINE	-	Lymphoma/myeloma differential for CNS mass lesion	No monoclonal protein
HIV, hepatitis B/C (CPT 87389)	-	ROUTINE	ROUTINE	-	Primary CNS lymphoma (PCNSL) differential; immunosuppression assessment; treatment implications	Negative
ESR / CRP (CPT 85652+86140)	-	ROUTINE	ROUTINE	-	Infection differential (abscess vs. metastasis); inflammatory markers	Normal
Cortisol (AM) (CPT 82533)	-	ROUTINE	ROUTINE	-	If pituitary metastasis suspected; before initiating dexamethasone if possible	Normal (>10 mcg/dL AM)
Prolactin	-	ROUTINE	ROUTINE	-	Pituitary metastasis differential	Normal

1C. Rare/Specialized (Refractory or Atypical)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
CSF cytology / flow cytometry (CPT 88104)	-	EXT	EXT	-	Leptomeningeal carcinomatosis evaluation; diagnostic if positive (sensitivity ~50% single LP, ~80% with repeat)	Negative; positive = leptomeningeal disease
CSF protein, glucose, cell count (CPT 84157+82945+89051)	-	EXT	EXT	-	Leptomeningeal disease (elevated protein, low glucose, lymphocytic pleocytosis)	Normal; elevated protein and low glucose suggest LMD
Circulating tumor DNA (ctDNA) / liquid biopsy	-	EXT	EXT	-	Unknown primary; molecular profiling when tissue biopsy not feasible; monitor treatment response	Detectable mutations guide therapy
Next-generation sequencing (NGS) - blood	-	EXT	EXT	-	Identify actionable mutations (EGFR, ALK, BRAF, HER2, KRAS, ROS1) when tissue insufficient	Actionable driver mutations
Paraneoplastic antibody panel	-	EXT	EXT	-	If clinical presentation suggests paraneoplastic syndrome mimicking or coexisting with metastatic disease	Negative; positive changes management
Methylmalonic acid, B12, folate	-	EXT	ROUTINE	-	Cognitive decline differential	Normal

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2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
CT head without contrast (CPT 70450)	STAT	STAT	-	STAT	Immediate in ED for acute presentation; identifies hemorrhage, mass effect, hydrocephalus	Mass lesion(s), hemorrhage, edema, midline shift, hydrocephalus; hemorrhagic metastases suggest melanoma, RCC, choriocarcinoma, thyroid	Pregnancy (benefit outweighs risk)
MRI brain with and without contrast (gadolinium) (CPT 70553)	STAT	STAT	URGENT	STAT	Within 24h of presentation; GOLD STANDARD for brain metastases; thin-cut (≤1mm) 3D T1 post-contrast	Number/size/location of metastases; ring-enhancement pattern; hemorrhagic component; leptomeningeal enhancement; dural-based vs. parenchymal	MRI-incompatible implants; GFR <30 (gadolinium risk); severe claustrophobia
CT chest/abdomen/pelvis with contrast (CPT 71260+74178)	URGENT	URGENT	ROUTINE	-	Within 24-48h if unknown primary; staging for known primary	Primary tumor identification; staging; additional metastatic disease	Contrast allergy; renal impairment
ECG (12-lead) (CPT 93000)	STAT	STAT	-	STAT	Baseline; pre-treatment; QTc for anti-emetics/targeted therapies	Normal	None
Chest X-ray (CPT 71046)	STAT	STAT	-	STAT	Lung primary (most common source of brain metastases); pulmonary metastases; aspiration if obtunded	Lung mass; effusion; lymphadenopathy	Pregnancy (shield)

2B. Extended

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
PET/CT (FDG) (CPT 78816)	-	ROUTINE	ROUTINE	-	Outpatient or during hospitalization; staging; unknown primary identification; ~85% sensitivity for primary site	Primary tumor; additional metastatic disease; lymph node involvement; treatment response assessment	Uncontrolled diabetes (glucose >200 impairs uptake); pregnancy
CT angiography (head) (CPT 70496)	URGENT	URGENT	-	URGENT	If hemorrhagic metastasis to evaluate vascularity; pre-surgical planning	Tumor vascularity; relationship to major vessels	Contrast allergy; renal impairment
MR spectroscopy (MRS)	-	ROUTINE	ROUTINE	-	Differentiating tumor from abscess or radiation necrosis; elevated choline:creatine ratio in tumor; lipid/lactate peak in necrosis	Elevated choline, reduced NAA in tumor; elevated lipid/lactate in necrosis	Same as MRI
MR perfusion (DSC or DCE)	-	ROUTINE	ROUTINE	-	Differentiating tumor recurrence from radiation necrosis; elevated rCBV in tumor	Elevated rCBV (>1.5-2.0) suggests tumor; low rCBV suggests radiation necrosis	Same as MRI
MRI spine (whole) with contrast (CPT 72156+72157+72158)	-	URGENT	ROUTINE	-	If spinal symptoms or leptomeningeal disease suspected; staging for drop metastases	Spinal metastases; leptomeningeal enhancement; cord compression	Same as MRI
Mammography / breast MRI (females)	-	ROUTINE	ROUTINE	-	Breast cancer is 2nd most common source of brain metastases in women	Breast mass or abnormality	Breast implants (mammography may be limited)
Stereotactic biopsy planning MRI	-	URGENT	ROUTINE	-	If tissue diagnosis needed and surgical resection not planned; fiducial/frameless navigation sequences	Biopsy trajectory planning; avoidance of eloquent cortex and vasculature	Same as MRI

2C. Rare/Advanced

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Thallium SPECT or FET-PET	-	-	EXT	-	Differentiating recurrent tumor vs. radiation necrosis when MR perfusion/spectroscopy equivocal	Increased uptake = tumor; decreased uptake = necrosis	Pregnancy
Functional MRI (fMRI)	-	-	EXT	-	Pre-surgical planning for metastases near eloquent cortex (motor, language areas)	Motor/language cortex mapping relative to lesion	Same as MRI
Diffusion tensor imaging (DTI) / Tractography	-	-	EXT	-	Pre-surgical planning; white matter tract relationship to tumor	Tract displacement vs. infiltration	Same as MRI
CT-guided biopsy (extracranial)	-	ROUTINE	ROUTINE	-	Biopsy accessible extracranial metastatic site rather than brain (safer, easier tissue acquisition)	Histopathologic diagnosis; molecular profiling	Coagulopathy; site-specific risks

Lumbar Puncture (if indicated)

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
LP (CPT 62270) with CSF cytology, flow cytometry, protein, glucose, cell count	-	URGENT	EXT	URGENT	If leptomeningeal disease suspected (cranial neuropathies, radiculopathy, headache, altered mentation without adequate parenchymal lesion to explain); MUST ensure no obstructive hydrocephalus or significant mass effect first	Cytology: malignant cells (50% sensitivity single LP; repeat improves to ~80%); elevated opening pressure; elevated protein (>50 mg/dL); low glucose (<40 mg/dL or <60% serum); lymphocytic pleocytosis	CONTRAINDICATED if significant mass effect, large posterior fossa lesion, obstructive hydrocephalus, midline shift >5mm (herniation risk); coagulopathy; local infection at LP site

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3. TREATMENT PROTOCOLS

3A. Acute/Emergent Treatment

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Dexamethasone (vasogenic edema) (CPT 96374)	IV	-	10 mg :: IV :: q6h :: Symptomatic edema: 10 mg IV loading dose, then 4 mg IV/PO q6h; Moderate symptoms: 4-8 mg/day; Severe/impending herniation: 10 mg IV bolus then 4-8 mg IV q6h (up to 16-24 mg/day); Taper as soon as clinically feasible over 2-4 weeks; GI prophylaxis with PPI (omeprazole 20 mg daily) while on steroids; Monitor glucose q6h initially	-	Dexamethasone is preferred corticosteroid (minimal mineralocorticoid effect, long half-life); symptomatic improvement in 24-72h; reduces vasogenic edema via BBB stabilization; no benefit in asymptomatic patients without edema (AVOID routine prophylactic use)	STAT	STAT	URGENT	STAT
Seizure management (acute)	IV	-	0.1 mg/kg :: IV :: - :: Active seizure: Lorazepam 0.1 mg/kg IV (max 4 mg), may repeat x1 in 5 min; Then: Levetiracetam 1000-1500 mg IV load (preferred - no drug interactions with chemotherapy) OR valproic acid 20-30 mg/kg IV load (avoid with hepatic metastases); Phenytoin/fosphenytoin only if above unavailable (interacts with many chemotherapies and targeted agents)	-	Levetiracetam preferred: no hepatic enzyme induction (does NOT reduce efficacy of steroids, chemotherapy, or targeted agents), renal elimination, broad spectrum; AAN guidelines do NOT recommend prophylactic AEDs in brain tumor patients without seizures	STAT	STAT	-	STAT
No prophylactic anticonvulsants	-	-	N/A :: - :: per protocol :: Do NOT start AEDs prophylactically in patients with brain metastases who have NOT had seizures; Applicable even peri-operatively (surgical prophylaxis may be used 7 days only per institutional protocol)	-	AAN Practice Parameter (Glantz et al., 2000; reaffirmed): No evidence supporting prophylactic AED use in brain tumor patients; side effects outweigh benefits; ASCO guideline concordant	STAT	STAT	ROUTINE	STAT
Airway/ICP management (obtunded patient)	IV	-	1-1.5 g/kg :: IV :: once :: GCS ≤8: Intubation; elevate HOB 30°; Acute herniation: Mannitol 1-1.5 g/kg IV bolus OR hypertonic saline (23.4% NaCl 30 mL via central line over 15 min or 3% NaCl 250 mL over 30 min); maintain PaCO2 30-35 mmHg (brief hyperventilation only as bridge to definitive treatment); Emergent neurosurgery consult for decompression	-	ICP management as bridge to definitive treatment (surgery/radiation); prolonged hyperventilation causes cerebral ischemia; osmotherapy reduces cerebral edema	STAT	-	-	STAT
DVT prophylaxis	SC	-	40 mg :: SC :: q8h :: SCDs (sequential compression devices) immediately on admission; Pharmacologic prophylaxis: enoxaparin 40 mg SQ daily or heparin 5000 units SQ q8h - START within 24-48h unless hemorrhagic metastasis or planned surgery within 24h; Post-craniotomy: restart pharmacologic DVT ppx within 24-48h per neurosurgery guidance	-	Brain tumor patients have 20-30% VTE risk; mechanical prophylaxis alone insufficient; pharmacologic prophylaxis does NOT significantly increase intracranial hemorrhage risk (Perry et al., 2009; AVERT trial)	-	STAT	-	STAT
Stress ulcer prophylaxis	PO	-	20 mg :: PO :: daily :: PPI (omeprazole 20 mg daily or pantoprazole 40 mg daily) while on dexamethasone; continue throughout steroid course	-	Combined corticosteroid + critical illness increases GI bleed risk	STAT	STAT	ROUTINE	STAT

3B. Definitive/Targeted Treatment

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Surgical resection	-	-	60% :: - :: - :: Indications: Single (or limited ≤3) accessible metastasis; need for tissue diagnosis; symptomatic mass effect not responding to steroids; large lesion (>3-4 cm) not suitable for SRS alone; good performance status (KPS ≥70); controlled systemic disease; life expectancy >3 months; Post-op: MRI within 24-48h to assess residual; SRS to cavity within 2-4 weeks to reduce local recurrence (50-60% → 15-20%)	-	Patchell et al. (1990): Surgery + WBRT > WBRT alone for single brain metastasis (median survival 40 vs. 15 weeks); Cavity SRS post-resection: Mahajan et al. (2017): local control improved with cavity SRS vs. observation	-	URGENT	-	-
Stereotactic radiosurgery (SRS)	-	-	N/A :: - :: once :: Indications: 1-4 metastases (most centers), up to 10-15 in select cases (JLGK0901); size ≤3-4 cm; Dose: Single fraction 15-24 Gy (dose based on size: ≤2cm: 20-24 Gy, 2.1-3cm: 18 Gy, 3.1-4cm: 15 Gy) OR fractionated SRS (3-5 fractions for larger lesions or eloquent location); Timing: Within 2-4 weeks of diagnosis; Serial MRI q2-3 months post-SRS	-	Yamamoto et al. (JLGK0901): SRS alone for 2-10 metastases non-inferior to 2-4 for survival; SRS vs. WBRT: better cognitive preservation (NCCTG N0574, Brown et al., 2016); SRS + HA-WBRT vs SRS alone per NRG-CC003	-	URGENT	ROUTINE	-
Whole-brain radiation therapy (WBRT)	-	-	20 mg :: - :: daily :: Indications: >10-15 metastases; leptomeningeal disease; poor surgical/SRS candidates; miliary/diffuse pattern; Standard: 30 Gy in 10 fractions (or 20 Gy in 5 fractions for poor prognosis); Hippocampal avoidance (HA-WBRT): Preferred when technically feasible (no metastases within 5mm of hippocampus): 30 Gy in 10 fractions with hippocampal sparing + memantine 20 mg daily starting with WBRT x 6 months	-	HA-WBRT + memantine (NRG-CC001, Brown et al., 2020): significantly less cognitive deterioration vs. standard WBRT + memantine at 4 and 6 months; Memantine alone (RTOG 0614): trend toward better cognitive function	-	URGENT	ROUTINE	-
Systemic therapy with CNS activity	-	-	80 mg :: - :: daily :: NSCLC with EGFR mutation: Osimertinib 80 mg daily (CNS response rate 91%); NSCLC with ALK rearrangement: Lorlatinib 100 mg daily (intracranial response 82%) or alectinib 600 mg BID (CNS response 81%); NSCLC with ROS1: Lorlatinib; Melanoma with BRAF V600: Dabrafenib + trametinib (intracranial response 58%) or encorafenib + binimetinib; Melanoma (any): Ipilimumab + nivolumab (intracranial response 46-57% in asymptomatic); HER2+ breast: Tucatinib + trastuzumab + capecitabine (HER2CLIMB: intracranial response 47%); Breast (HR+): Abemaciclib (some CNS activity); RCC: Nivolumab + ipilimumab or cabozantinib	-	CNS-penetrant systemic therapy increasingly used as upfront or adjunct to SRS; may defer radiation in asymptomatic patients with actionable mutations and small metastases; Always coordinate with medical oncology	-	ROUTINE	ROUTINE	-
Corticosteroid taper	-	-	2 mg :: - :: once :: Begin taper once definitive treatment initiated and symptoms improving; Taper schedule: Reduce by 2 mg every 3-5 days (from 16 mg/day: 16→12→8→6→4→2→1→off); Slower taper if symptoms recur; Monitor for adrenal insufficiency if >3 weeks of steroid use	-	Prolonged steroids cause significant morbidity: hyperglycemia, myopathy (steroid myopathy can be debilitating), immunosuppression, osteoporosis, PJP risk, insomnia, psychiatric effects, GI bleeding	-	ROUTINE	ROUTINE	-

3C. Adjunctive Treatment

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Levetiracetam (post-seizure maintenance)	IV	-	500-1500 mg :: IV :: BID :: 500-1500 mg PO/IV BID (start 500 mg BID, titrate to seizure control); Renal dosing if GFR <50; No drug interactions with chemotherapy, targeted therapy, or steroids	-	Preferred AED in brain tumor patients due to no CYP enzyme induction; does not reduce efficacy of dexamethasone, temozolomide, or targeted agents	-	STAT	ROUTINE	STAT
PJP prophylaxis	PO	-	20 mg :: PO :: daily :: If dexamethasone >20 mg/week AND concomitant temozolomide or immunosuppression: TMP-SMX 1 DS tablet 3x/week (Mon/Wed/Fri) OR atovaquone 1500 mg daily if sulfa allergic	-	Risk of Pneumocystis with prolonged corticosteroids + additional immunosuppression	-	ROUTINE	ROUTINE	-
Glucose management (steroid-induced)	-	-	180 mg :: - :: q6h :: Fingerstick glucose q6h while on dexamethasone; Sliding scale insulin initially; Basal-bolus insulin if persistently >180 mg/dL; Anticipate glucose elevation typically 4-8 hours after steroid dose; May need 2-3x baseline insulin requirements	-	Dexamethasone causes significant hyperglycemia in 50-60% of patients; uncontrolled hyperglycemia worsens outcomes	STAT	STAT	ROUTINE	STAT
Calcium/Vitamin D	PO	-	1000-1200 mg :: PO :: daily :: Calcium 1000-1200 mg + Vitamin D 800-1000 IU daily while on prolonged steroids (>2 weeks)	-	Steroid-induced osteoporosis prevention	-	ROUTINE	ROUTINE	-
Anti-emetics (for radiation/chemotherapy)	IV	-	4-8 mg :: IV :: q8h :: Ondansetron 4-8 mg IV/PO q8h PRN; Dexamethasone itself is anti-emetic; Avoid metoclopramide in brain metastases patients (extrapyramidal effects)	-	Nausea common with elevated ICP and with radiation therapy	-	ROUTINE	ROUTINE	-
Memantine (with WBRT)	-	-	5 mg :: - :: daily :: 5 mg daily x1 week → 5 mg BID x1 week → 10 mg AM + 5 mg PM x1 week → 10 mg BID; Continue for 6 months total; Start day 1 of WBRT	-	RTOG 0614 and NRG-CC001: cognitive protection during WBRT; NMDA receptor antagonist reduces excitotoxic neuronal injury from radiation	-	ROUTINE	ROUTINE	-

3D. Medications to AVOID or Use with Caution

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Prophylactic anticonvulsants (in patients without seizures)	-	-	-	-	-	-	-	-	-	-
Phenytoin / Carbamazepine / Phenobarbital (enzyme-inducing AEDs)	-	-	-	-	-	-	-	-	-	-
Bevacizumab (concurrent with surgery)	-	-	-	-	-	-	-	-	-	-
Anticoagulation (full-dose, peri-operative)	-	-	-	-	-	-	-	-	-	-
Methotrexate (high-dose, with brain radiation)	-	-	-	-	-	-	-	-	-	-
Live vaccines (while on dexamethasone or chemotherapy)	-	-	-	-	-	-	-	-	-	-
Lumbar puncture (with large posterior fossa lesion / significant mass effect)	-	-	-	-	-	-	-	-	-	-

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4. OTHER RECOMMENDATIONS

4A. Essential

Recommendation	ED	HOSP	OPD	ICU	Details
Neurosurgery consultation	STAT	STAT	ROUTINE	STAT	For surgical candidacy evaluation (single/oligometastases, mass effect, tissue diagnosis need); emergency for herniation/acute hydrocephalus
Radiation oncology consultation	-	URGENT	ROUTINE	-	SRS vs. WBRT vs. HA-WBRT decision; coordinate with surgery (post-resection cavity SRS within 2-4 weeks)
Medical oncology consultation	-	URGENT	ROUTINE	-	Systemic therapy options; molecular profiling for targeted agents; staging; prognosis; clinical trial eligibility
Multidisciplinary tumor board	-	URGENT	ROUTINE	-	Brain metastases management requires coordinated neurosurgery, radiation oncology, medical oncology, neuroradiology input; optimal sequencing of treatments
Goals of care discussion	-	URGENT	ROUTINE	URGENT	Discuss prognosis, treatment intent (curative vs. palliative), quality of life, code status; especially important for patients with limited systemic options or poor functional status (KPS <50)
Pathology review with molecular profiling	-	URGENT	ROUTINE	-	Confirm tissue diagnosis; molecular testing (NGS panel for EGFR, ALK, ROS1, BRAF, HER2, KRAS G12C, NTRK, RET, MET); PD-L1 (TPS and CPS); hormone receptors (breast); BRAF V600 (melanoma)
Fall precautions	STAT	STAT	ROUTINE	STAT	Brain metastases patients at high risk for falls (focal deficits, seizures, steroid myopathy, cognitive impairment); Remove fall hazards; PT/OT evaluation
Driving restrictions	-	ROUTINE	ROUTINE	-	Advise against driving if seizures, visual field deficits, significant cognitive impairment, or posterior fossa lesions affecting coordination; State-specific reporting requirements

4B. Extended

Recommendation	ED	HOSP	OPD	ICU	Details
Palliative care consultation	-	ROUTINE	ROUTINE	-	Symptom management; goals of care facilitation; advance care planning; coordination of hospice if appropriate
Neuropsychology evaluation	-	-	ROUTINE	-	Baseline cognitive assessment before radiation treatment; monitor cognitive decline; guide rehabilitation
Physical/occupational therapy	-	ROUTINE	ROUTINE	-	Functional assessment; mobility training; ADL assistance; steroid myopathy mitigation (exercise program)
Speech-language pathology	-	ROUTINE	ROUTINE	-	If aphasia, dysarthria, dysphagia from metastasis location; swallow evaluation if posterior fossa lesion or obtunded
Social work / case management	-	ROUTINE	ROUTINE	-	Insurance authorization for SRS/radiation; transportation; caregiver support; disability paperwork
Genetic counseling	-	-	ROUTINE	-	If young patient or cancer predisposition syndrome suspected (Li-Fraumeni, BRCA, Lynch)
Clinical trials evaluation	-	ROUTINE	ROUTINE	-	Active brain metastases trials (immunotherapy combinations, targeted agents, radiosensitizers); NCI clinical trials database; institutional trials
Ophthalmology consultation	-	ROUTINE	ROUTINE	-	If visual complaints, papilledema, metastasis near visual pathways; formal visual fields testing

4C. Atypical/Refractory

Recommendation	ED	HOSP	OPD	ICU	Details
Repeat biopsy / resection	-	URGENT	ROUTINE	-	If radiation necrosis vs. recurrence unclear after advanced imaging (MR perfusion, MRS, PET); tissue diagnosis changes management
Ommaya reservoir placement	-	ROUTINE	ROUTINE	-	Recurrent leptomeningeal disease requiring intrathecal chemotherapy; avoids repeated lumbar punctures
Intrathecal chemotherapy	-	ROUTINE	ROUTINE	-	Leptomeningeal carcinomatosis: methotrexate 12 mg IT or cytarabine (liposomal) 50 mg IT q2 weeks; via Ommaya reservoir; limited efficacy data
Laser interstitial thermal therapy (LITT)	-	ROUTINE	ROUTINE	-	MRI-guided laser ablation for recurrent metastases in deep or eloquent locations; radiation necrosis treatment
Re-irradiation (SRS for recurrence)	-	-	ROUTINE	-	SRS for recurrent metastases after prior SRS or WBRT; consider cumulative dose to normal brain; risk of radiation necrosis increases
Bevacizumab for radiation necrosis	-	ROUTINE	ROUTINE	-	7.5 mg/kg IV q3 weeks for symptomatic radiation necrosis refractory to steroids; significant improvement in ~65% of patients (Levin et al., 2011)
Hospice referral	-	ROUTINE	ROUTINE	-	Poor prognosis (DS-GPA <1.0), declining functional status, exhausted treatment options, patient/family preference for comfort-focused care

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═══════════════════════════════════════════════════════════════ SECTION B: SUPPORTING INFORMATION ═══════════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS

Primary Differential Diagnoses

Diagnosis	Key Differentiating Features	Distinguishing Studies
Primary brain tumor (GBM, astrocytoma)	Usually single; irregular enhancement; often involves corpus callosum (butterfly GBM); no known systemic cancer; infiltrative margins; surrounding FLAIR/T2 more extensive; restricted diffusion at tumor margins	MRI pattern; MR spectroscopy (elevated choline:creatine, reduced NAA); biopsy (IDH, MGMT, 1p19q); no systemic disease on staging CT/PET
Primary CNS lymphoma (PCNSL)	Periventricular location; homogeneously enhancing; restricted diffusion; may be multifocal; immunocompromised patients; responds dramatically to corticosteroids (may "disappear" = ghost tumor); typically does NOT ring-enhance unless HIV	MRI with diffusion restriction; AVOID steroids before biopsy if possible (may render biopsy non-diagnostic); CSF flow cytometry; vitreous biopsy if ocular involvement; HIV testing; slit lamp exam
Brain abscess	Ring-enhancing lesion with restricted diffusion on DWI (bright on DWI, dark on ADC in the cavity — metastases typically do NOT show central restricted diffusion); fever, elevated WBC; recent sinusitis/otitis/dental procedure/endocarditis; thin smooth enhancing rim; satellite lesions	DWI: central restricted diffusion is KEY distinguishing feature; MR spectroscopy: amino acid peaks (succinate, acetate, lactate); blood cultures; echocardiogram; source identification
Toxoplasmosis (immunocompromised)	HIV/AIDS (CD4 <100); multiple ring-enhancing lesions; basal ganglia predilection; eccentric target sign; edema/mass effect	Toxoplasma IgG (serum); CD4 count; empiric treatment trial (response in 10-14 days supports diagnosis); if no response → biopsy; Thallium SPECT (increased uptake = lymphoma, not toxoplasmosis)
Demyelinating disease (tumefactive MS, ADEM)	Incomplete ring enhancement (open ring sign); younger patients; clinical dissemination in time/space; less mass effect relative to lesion size; leading edge enhancement	MRI: open ring enhancement, T2/FLAIR lesions in MS-typical locations; CSF: oligoclonal bands; MOG/AQP4 antibodies; clinical response to steroids
Radiation necrosis	History of prior brain radiation (typically 6-24 months post-treatment but can occur later); enhancing lesion at site of prior radiation; difficult to distinguish from recurrent tumor on conventional MRI	MR perfusion: LOW rCBV (vs. tumor with HIGH rCBV); MR spectroscopy: elevated lipid/lactate, low choline; PET: low FDG uptake (vs. tumor with high uptake); biopsy if equivocal
Neurocysticercosis	Travel/residence in endemic area (Latin America, sub-Saharan Africa, Southeast Asia); cystic lesions with scolex (dot within cyst); often calcified in chronic phase; seizure is common presentation	MRI: cystic lesion with scolex; CT: calcified granulomas; serology (cysticercosis antibodies); stool ova/parasites
Cerebral infarct (subacute)	Vascular territory distribution; ring enhancement at 1-4 weeks post-stroke (luxury perfusion); clinical history of acute onset; DWI abnormalities conforming to vascular territory	Timing of enhancement (subacute strokes enhance transiently); vascular territory distribution; DWI/ADC map evolution; clinical history of acute onset

Red Flags Requiring Urgent Reassessment

Red Flag	Concern	Action
Rapid neurologic decline	Hemorrhage into metastasis; acute hydrocephalus; herniation	STAT CT head; neurosurgery STAT; consider intubation
New seizure (first-time)	Peri-tumoral irritation; hemorrhage; edema worsening; leptomeningeal spread	CT head (rule out hemorrhage); start AED (levetiracetam); re-image with MRI
Worst headache of life / thunderclap	Hemorrhagic metastasis (especially melanoma, RCC); pituitary apoplexy from pituitary metastasis	STAT CT head; CT angiography if SAH pattern
Fever + mental status changes	Brain abscess (metastasis can be misdiagnosed as abscess and vice versa); infection in immunocompromised patient; central fever from brain lesion	Blood cultures; CT head; LP if safe; broad-spectrum antibiotics if infection suspected
Acute vision loss	Pituitary metastasis with apoplexy; optic nerve/chiasm compression	STAT MRI; ophthalmology/neurosurgery STAT
Progressive bilateral leg weakness	Spinal cord compression from spinal metastases; leptomeningeal disease affecting cauda equina	STAT MRI whole spine; dexamethasone 10 mg IV; neurosurgery/radiation oncology STAT
Cushing syndrome features (steroid complications)	Prolonged dexamethasone; immunosuppression; hyperglycemia; myopathy; osteoporosis	Taper steroids; manage complications; alternative edema management (bevacizumab for radiation necrosis)

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6. MONITORING PARAMETERS

Acute Phase Monitoring (First 72h)

Parameter	Frequency	Target	Action if Abnormal
Neurologic checks (GCS, pupil reactivity, motor exam, speech)	q1-2h in ICU; q2-4h on floor	Stable or improving exam	Stat CT head if decline; neurosurgery alert; consider increasing dexamethasone or osmotherapy
Blood glucose	q6h (q1h if insulin drip)	140-180 mg/dL	Sliding scale → basal-bolus insulin; typically requires 2-3x baseline insulin on dexamethasone
Blood pressure	Continuous in ICU; q4h on floor	SBP <160 (avoid hypertensive hemorrhage into metastasis)	Antihypertensives PRN; avoid excessive hypotension (SBP >100 to maintain cerebral perfusion)
Fluid balance / I&O	q8h	Euvolemia	Hyponatremia common (SIADH, cerebral salt wasting); free water restriction if SIADH
Sodium	q6-8h initially	135-145 mEq/L	If <130: fluid restrict; if <125 or symptomatic: 3% NaCl; if rapidly dropping: urgent sodium correction
Seizure monitoring	Continuous observation; consider cEEG if altered mental status	No seizures; no subclinical seizures	AED initiation/adjustment; neurology consultation; continuous EEG monitoring
Pain assessment	q4h	NRS <4/10	Acetaminophen 650-1000 mg q6h; dexamethasone (reduces headache from edema); opioids PRN for moderate-severe

Subacute/Outpatient Monitoring

Parameter	Frequency	Target	Action if Abnormal
MRI brain with contrast	q2-3 months for first year post-treatment, then q3-4 months year 2, then q6 months	Stable/decreasing lesion size; no new metastases	New/progressive lesions: repeat multidisciplinary discussion; salvage SRS, surgery, systemic therapy change
Neurologic examination	Each clinic visit (q2-4 weeks during treatment, q1-3 months maintenance)	Stable or improved	New deficits: urgent MRI; consider tumor progression vs. radiation necrosis vs. new metastasis
KPS / ECOG performance status	Each visit	KPS ≥70 / ECOG 0-2 for active treatment	KPS <50 / ECOG ≥3: reassess goals of care; transition to supportive/palliative care
Steroid taper progress	Each visit	Off dexamethasone or minimal dose	Steroid-dependent edema: consider bevacizumab, re-irradiation, or resection to enable taper
Blood glucose (while on steroids)	Daily fingerstick; HbA1c monthly	Fasting <130; random <180	Insulin titration; endocrine consultation if difficult to control
CBC (if on chemotherapy)	Per chemotherapy cycle protocol; typically q2-3 weeks	ANC >1500, platelets >100,000	Hold/dose-reduce chemotherapy; growth factor support
Hepatic/renal function	Monthly during systemic therapy	Normal	Dose adjustment; drug-specific monitoring per protocol
Neurocognitive screening	q3-6 months; MoCA or formal neuropsychological testing	Stable cognitive function	Cognitive rehabilitation; medication review; assess for depression; differentiate radiation injury vs. progression
Depression/anxiety screening (PHQ-9)	Each visit	PHQ-9 <5	SSRI (avoid CYP interactions); psychology referral; supportive care

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7. DISPOSITION CRITERIA

Admission Criteria

Level of Care	Criteria
ICU admission	GCS ≤12; signs of herniation (pupil asymmetry, posturing, Cushing triad); acute hemorrhage into metastasis with neurologic decline; post-craniotomy (first 24h); status epilepticus; respiratory compromise requiring intubation; hemodynamic instability
General neurology/neurosurgery floor	New diagnosis requiring workup and treatment planning; symptomatic edema requiring IV dexamethasone; post-seizure requiring monitoring and AED optimization; post-craniotomy (step-down from ICU); functional decline requiring inpatient rehabilitation planning
Observation (≤24h)	Known brain metastases with mild symptom change; MRI revealing progression but patient clinically stable; steroid dose adjustment with monitoring

Discharge Criteria

Criterion	Details
Neurologic stability	Stable or improving neurologic exam for ≥24h on current steroid dose; no new deficits
Seizure control	Seizure-free ≥24h on oral AED; no breakthrough seizures; AED levels therapeutic if applicable
Steroid plan	Oral dexamethasone regimen established with clear taper schedule; glucose management plan in place
Pain control	Headache adequately controlled on oral medications
Treatment plan established	Multidisciplinary plan documented (surgery, radiation, systemic therapy); appointments scheduled within 1-2 weeks
Functional safety	Safe ambulation (with or without assistive device); safe swallowing; able to perform basic ADLs or adequate caregiver support
VTE plan	Transition to pharmacologic prophylaxis or therapeutic anticoagulation plan if VTE occurred
Follow-up arranged	Neurosurgery (1-2 weeks if post-op), radiation oncology (1-2 weeks for SRS/WBRT planning), medical oncology (1-2 weeks), PCP (1 week for steroid monitoring); MRI brain scheduled at appropriate interval
Patient/family education	Understanding of diagnosis, treatment plan, steroid side effects, seizure precautions, when to return to ED (acute headache, new weakness, seizure, vision changes, fever)

Discharge Prescriptions Checklist

Medication	Details
Dexamethasone	Taper schedule clearly documented (e.g., 4 mg q6h x 3 days → 4 mg q8h x 3 days → 4 mg q12h x 3 days → 4 mg daily x 3 days → 2 mg daily x 3 days → stop)
PPI	Omeprazole 20 mg daily or pantoprazole 40 mg daily while on steroids
AED (if seizure occurred)	Levetiracetam dose and frequency; DO NOT start if no seizure history
Insulin (if needed)	Sliding scale or basal-bolus regimen for steroid-induced hyperglycemia; glucometer and supplies
Calcium + Vitamin D	If steroids >2 weeks anticipated
DVT prophylaxis (if applicable)	Enoxaparin transition plan if VTE occurred
Analgesics	Acetaminophen; limited opioid prescription if needed
TMP-SMX (if applicable)	If on high-dose steroids + chemotherapy (PJP prophylaxis)

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8. EVIDENCE & REFERENCES

Key Guidelines

Guideline	Source	Year	Key Recommendation
Management of Brain Metastases	Congress of Neurological Surgeons (CNS) / AANS Systematic Review	2019	Surgery for single accessible metastasis with mass effect; SRS for limited brain metastases (1-4); WBRT for multiple (>10-15) or leptomeningeal disease; avoid prophylactic AEDs
Brain Metastases Molecular Testing	NCCN Central Nervous System Cancers	v1.2025	Comprehensive molecular profiling for actionable targets (EGFR, ALK, ROS1, BRAF, HER2, KRAS G12C, NTRK, RET, MET, PD-L1); guide systemic therapy selection
Prophylactic Anticonvulsants	AAN Practice Parameter (Glantz et al.)	2000 (reaffirmed)	Routine prophylactic AEDs NOT recommended in brain tumor patients without seizures
Hippocampal Avoidance WBRT	NRG-CC001 (Brown et al.)	2020	HA-WBRT + memantine superior to standard WBRT + memantine for cognitive preservation
SRS for Multiple Brain Metastases	JLGK0901 (Yamamoto et al.)	2014	SRS for 5-10 metastases non-inferior to 2-4 for overall survival
Cognitive Outcomes SRS vs. WBRT	NCCTG N0574 (Brown et al.)	2016	SRS alone superior to SRS + WBRT for cognitive preservation; no overall survival difference

Landmark Studies

Study	Finding	Impact
Patchell et al. (1990)	Surgery + WBRT vs. WBRT alone for single brain metastasis: median survival 40 vs. 15 weeks; lower recurrence at original site (20% vs. 52%)	Established surgery as standard for single brain metastasis
Patchell et al. (1998)	Post-operative WBRT reduced brain recurrence (18% vs. 70%) but no survival benefit; improved neurologic death	Supported adjuvant radiation after surgery; now often SRS to cavity instead of WBRT
Mahajan et al. (2017) - MD Anderson	SRS to surgical cavity vs. observation: 12-month local recurrence 28% vs. 59% (HR 0.46)	Established post-operative cavity SRS as standard of care
Brown et al. (2016) - NCCTG N0574	SRS alone vs. SRS + WBRT: cognitive deterioration at 3 months 64% vs. 92%; no OS difference	Shifted practice toward SRS alone with surveillance MRI rather than WBRT
Yamamoto et al. (2014) - JLGK0901	SRS for 5-10 vs. 2-4 brain metastases: similar overall survival (10.8 vs. 10.8 months)	Expanded SRS indications to higher numbers of metastases
Brown et al. (2020) - NRG-CC001	HA-WBRT + memantine vs. WBRT + memantine: less cognitive deterioration at 4 months (59% vs. 68%) and 6 months; less decline in executive function and memory	HA-WBRT + memantine = new standard when WBRT indicated
Tawbi et al. (2018) - CheckMate 204	Ipilimumab + nivolumab in melanoma brain metastases: intracranial response 57% in asymptomatic patients	Established immunotherapy as upfront option for melanoma brain metastases
Reungwetwattana et al. (2018) - FLAURA CNS analysis	Osimertinib CNS response rate 91% in EGFR-mutant NSCLC with brain metastases vs. 68% standard EGFR TKI	Established osimertinib as preferred first-line for EGFR+ NSCLC with brain metastases
Murthy et al. (2020) - HER2CLIMB	Tucatinib + trastuzumab + capecitabine: intracranial response 47%; CNS-PFS 9.9 vs. 4.2 months; OS benefit in brain metastases subgroup	Established tucatinib combination as standard for HER2+ breast cancer brain metastases
Perry et al. (2010) - PRODIGE	Dalteparin vs. placebo in malignant glioma: no increase in intracranial hemorrhage with anticoagulation; VTE reduction	Supported pharmacologic DVT prophylaxis in brain tumor patients
Levin et al. (2011)	Bevacizumab for radiation necrosis: significant radiographic and clinical improvement in ~65% of patients	Established bevacizumab as treatment option for symptomatic radiation necrosis refractory to steroids

Grading Scales

Diagnosis-Specific Graded Prognostic Assessment (DS-GPA)

Component	Score = 0	Score = 0.5	Score = 1.0
Age (years)	>60	50-60	<50
KPS	<70	70-80	90-100
Number of CNS metastases	>3	2-3	1
Extracranial metastases	Present	-	Absent

Note: DS-GPA varies by primary tumor type. The above is the general framework. Lung-molGPA incorporates molecular markers (EGFR, ALK). Melanoma-molGPA incorporates BRAF status. Breast-GPA incorporates receptor status (HR/HER2). Always use the disease-specific GPA tool.

DS-GPA Score (general)	Median Survival
0-1.0	2.6 months
1.5-2.0	4.4 months
2.5-3.0	9.4 months
3.5-4.0	14.8 months

Recursive Partitioning Analysis (RPA) Classification (RTOG)

Class	Criteria	Median Survival
Class I	KPS ≥70, age <65, controlled primary, no extracranial metastases	7.1 months
Class II	All other patients	4.2 months
Class III	KPS <70	2.3 months

Karnofsky Performance Status (KPS)

Score	Description
100	Normal, no complaints
90	Able to carry on normal activity; minor signs/symptoms
80	Normal activity with effort; some signs/symptoms
70	Cares for self; unable to carry on normal activity or active work
60	Requires occasional assistance but cares for most needs
50	Requires considerable assistance and frequent medical care
40	Disabled; requires special care and assistance
30	Severely disabled; hospitalization indicated, death not imminent
20	Very sick; active supportive treatment needed
10	Moribund

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APPENDICES

Appendix A: Most Common Primary Sites of Brain Metastases

Primary Cancer	Approximate Frequency	Typical MRI Features	Key Molecular Targets
Lung (NSCLC)	40-50% of brain metastases	Multiple; any location; may hemorrhage; often ring-enhancing	EGFR, ALK, ROS1, BRAF V600E, KRAS G12C, MET, RET, NTRK, PD-L1
Lung (SCLC)	10-15%	Multiple; tend to be small; prophylactic cranial irradiation (PCI) standard in limited-stage SCLC with response	PD-L1; limited targeted options
Breast	15-25%	HER2+ and triple-negative most commonly metastasize to brain; may be hemorrhagic; dural-based possible	HER2 (tucatinib, T-DXd), HR+ (CDK4/6 inhibitors — limited CNS data), PD-L1 (triple-negative)
Melanoma	5-15%	Hemorrhagic (T1-hyperintense on pre-contrast MRI due to melanin and blood); multiple; any location	BRAF V600 (dabrafenib + trametinib), PD-1 + CTLA-4 (ipilimumab + nivolumab)
Renal cell carcinoma	5-10%	Highly vascular; hemorrhagic; large lesions; significant surrounding edema	TKIs (cabozantinib), immunotherapy (ipilimumab + nivolumab)
Colorectal	3-5%	Posterior fossa predilection; typically late in disease	KRAS, BRAF, MSI-H/dMMR (pembrolizumab)
Unknown primary	5-10%	Variable	Comprehensive molecular profiling essential

Appendix B: Hemorrhagic Brain Metastases — High-Risk Primaries

Mnemonic: "MR CT" — Melanoma, Renal cell carcinoma, Choriocarcinoma, Thyroid

Primary	Hemorrhage Risk	Management Considerations
Melanoma	Very high (40-50% hemorrhagic)	T1 hyperintense from melanin + blood; SRS preferred over surgery when feasible (hemorrhage risk during resection); immunotherapy may be used upfront
Renal cell carcinoma	High (30-40% hemorrhagic)	Highly vascular; pre-operative embolization considered; hemorrhage may be presenting symptom
Choriocarcinoma	Very high	β-hCG markedly elevated; chemotherapy highly effective; hemorrhage may be initial presentation
Thyroid (papillary/follicular)	Moderate	Often indolent; radioactive iodine does NOT treat brain metastases (insufficient BBB penetration); surgery or SRS needed
Lung (NSCLC on anticoagulation)	Moderate	Stop anticoagulation if hemorrhagic metastasis; reverse if on warfarin/DOACs

Appendix C: CNS-Penetrant Systemic Therapies — Quick Reference

Cancer Type	Drug	CNS Response Rate	Key Trial
NSCLC, EGFR+	Osimertinib 80 mg daily	91%	FLAURA (Reungwetwattana 2018)
NSCLC, ALK+	Lorlatinib 100 mg daily	82%	CROWN (Shaw 2020)
NSCLC, ALK+	Alectinib 600 mg BID	81%	ALEX (Peters 2017)
NSCLC, ROS1+	Lorlatinib 100 mg daily	~60%	Phase II data
Melanoma, BRAF+	Dabrafenib 150 mg BID + trametinib 2 mg daily	58%	COMBI-MB (Davies 2017)
Melanoma, any	Ipilimumab 3 mg/kg + nivolumab 1 mg/kg	46-57%	CheckMate 204 (Tawbi 2018)
HER2+ breast	Tucatinib + trastuzumab + capecitabine	47%	HER2CLIMB (Murthy 2020)
HER2+ breast	Trastuzumab deruxtecan (T-DXd)	63.9%	DESTINY-Breast03 (Cortés 2022)
Triple-negative breast	Sacituzumab govitecan	Limited CNS data	ASCENT (exploratory)
RCC	Cabozantinib 60 mg daily	~55% (retrospective)	Retrospective series
RCC	Ipilimumab + nivolumab	~28% (brain met subgroup)	CheckMate 214 (subgroup)

Appendix D: Treatment Algorithm — Decision Framework

BRAIN METASTASES DIAGNOSED
         │
         ├── Acute presentation (symptomatic edema, obtundation, herniation)?
         │         YES → Dexamethasone 10 mg IV → ICU if herniation → Emergent neurosurgery
         │         NO → Dexamethasone only if symptomatic edema present
         │
         ├── Number of metastases?
         │         │
         │         ├── 1 (single)
         │         │     ├── Surgically accessible + mass effect → Surgery → Cavity SRS
         │         │     ├── Not surgical candidate → SRS (single fraction or fractionated)
         │         │     └── With actionable mutation → Consider systemic first (e.g., osimertinib, ipi/nivo)
         │         │
         │         ├── 2-4 (oligometastases)
         │         │     ├── All ≤3-4 cm → SRS (each lesion)
         │         │     ├── 1 large + others small → Surgery for large + SRS for others
         │         │     └── With actionable mutation → Systemic + SRS
         │         │
         │         ├── 5-15
         │         │     ├── Select patients → SRS (JLGK0901 data supports up to 10-15)
         │         │     ├── Good systemic options → Systemic therapy + SRS
         │         │     └── Poor SRS candidate → HA-WBRT + memantine
         │         │
         │         └── >15 or miliary/diffuse
         │               └── HA-WBRT + memantine (if hippocampus-sparing feasible)
         │                   OR standard WBRT + memantine
         │
         ├── Molecular profiling?
         │         ├── EGFR+ NSCLC → Osimertinib (may defer radiation for small, asymptomatic)
         │         ├── ALK+ NSCLC → Lorlatinib or alectinib
         │         ├── BRAF+ melanoma → Dabrafenib + trametinib ± SRS
         │         ├── Melanoma (any) → Ipilimumab + nivolumab ± SRS
         │         ├── HER2+ breast → Tucatinib combo or T-DXd ± SRS
         │         └── No actionable target → Radiation + standard systemic
         │
         └── Surveillance post-treatment
                   └── MRI brain q2-3 months year 1 → q3-4 months year 2 → q6 months ongoing
                       New/progressive lesion → Salvage SRS, surgery, or systemic change
                       Suspected radiation necrosis → Advanced imaging → Bevacizumab if confirmed

Appendix E: Steroid Dosing and Taper Guide

Clinical Scenario	Initial Dexamethasone Dose	Duration Before Taper	Taper Schedule
Mild symptoms, small edema	4 mg/day (2 mg BID)	3-5 days	Reduce by 1 mg every 3-5 days
Moderate symptoms	8-12 mg/day (4 mg q6-8h)	5-7 days	Reduce by 2 mg every 3-5 days
Severe edema / mass effect	16 mg/day (4 mg q6h)	7-14 days	Reduce by 2-4 mg every 3-5 days
Impending herniation	10 mg IV bolus → 4-8 mg q6h (up to 24 mg/day)	Until definitive treatment	Taper after surgery/radiation with clinical monitoring
Post-SRS	4-8 mg/day starting day of SRS	3-7 days	Rapid taper over 5-7 days if no worsening
Steroid-dependent (cannot taper)	Minimum effective dose	Ongoing	Consider bevacizumab, re-irradiation, or resection to enable taper

Key steroid complications to monitor: Hyperglycemia (50-60%), insomnia, myopathy (proximal weakness — may mimic disease progression), immunosuppression (PJP risk), GI bleeding, osteoporosis, psychiatric effects (mania, psychosis — usually dose-related), adrenal suppression (if >3 weeks — taper slowly, do not abruptly stop).

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