Participant Screening

• Age ≥ 18 years
• Non-small cell lung cancer (NSCLC) with somatic activating mutation in EGFR diagnosis, confirmed at enrolling institution
• At least one intact brain metastasis at baseline prior to TKI therapy initiation, visible on MRI brain with contrast (but without a minimum diameter requirement)
• Either TKI-naïve or started TKI ≤ 3-months prior (with documented start date and available imaging prior to TKI start)

Participant

Screening

• Unable to undergo contrast-enhanced MRI brain
• Prior brain-directed radiotherapy
• Evidence of leptomeningeal disease on MRI total spine and/or lumbar puncture cytology. The latter are not mandated by protocol but are rather at the discretion of the treating medical team as clinically indicated.
• Neurologic symptoms or presence of a lesion in the brainstem, motor strip, or other eloquent brain area that is felt to warrant immediate intervention with SRS
• Active hematologic malignancy or a second solid tumor histology with known CNS tropism
• Patients who have undergone a therapeutic craniotomy for resection of one or more symptomatic brain metastasis are ineligible unless one or more additional intact BM remain unresected, and meets size criteria (e.g., a patient with removal of a 3cm symptomatic brain metastasis, but has an additional visible lesion remaining post-operatively, remains eligible for the study).
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
• Pregnant women or women who are breastfeeding or of childbearing potential. If the risk of contraception exists, male and female subjects must use highly effective contraception throughout the study and for at least 3 months after last treatment. Highly effective contraception includes either 2 barrier methods (diaphragm, condom by the partner, copper intrauterine device, sponge, or spermicide), or 1 barrier method and 1 hormonal method (any oral, subcutaneous, intrauterine, or intramuscular registered and marketed contraceptive agent that contains an estrogen and/or a progesterone agent)

Participant Inclusion Criteria: Randomization

- Presence of detectable and non-progressing BM lesions on imaging consistent with viable residual disease

Participant