Almonertinib is a three-generation epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI), which has shown competitive potential in the second-line treatment against first-generation TKIs. This study intends to assess the efficacy and safety of stereotactic radiosurgery with sequential almonertinib in treatment-naive EGFR-mutant NSCLC patients with brain metastases.

Inclusion Criteria:

1. Histologically or pathologically confirmed non-small-cell lung cancer (adenocarcinoma).
2. The presence of radiographically definite brain metastases and intracranial foci measurable according to the RANO-BM criteria.
3. The number of brain metastases ≤ 10, the volume of individual metastases ≤ 15 cc, the diameter of individual metastases ≤ 30 mm, the diameter of metastases in the brainstem ≤ 5 mm, distance of the foci from the optic nerve, or optic cross > 5 mm.
4. EGFR-sensitive mutations (include 19del or L858R mutation or coexist with other types of EGFR mutation).
5. Comply with the indications and drug instructions for first-line treatment with a third-generation EGFR-TKI.
6. Have not received systemic antineoplastic therapy, excluding neoadjuvant, adjuvant, or synchronous chemotherapy more than 6 months prior to enrollment.
7. Asymptomatic or mildly symptomatic brain metastases (e.g., headache, nausea, or seizures for which dexamethasone/analgesic/antiepileptic medication is effective and sustained at a steady dose for 3 days or more).
8. Age ≥ 18 years.
9. Eastern Cooperative Oncology Group (ECOG) performance status(PS) score ≤ 2.
10. Survival is expected to be ≥ 6 months.
11. Women must use contraception after surgical sterilization, after sterilization, or during and for three months after treatment.
12. With informed consent signed.

Exclusion Criteria:

1. Previous treatment with almonertinib or other EGFR-TKI.
2. Patients with symptomatic brain metastases resulting in neurological deficits (not including headaches, nausea, or controlled seizures).
3. Multiple sclerosis.
4. Pacemakers implanted in the body or metals that cannot be examined by MRI.
5. Allergy to magnetic resonance contrast agents.
6. Brain metastases requiring surgical decompression.
7. Meningeal metastases.
8. Previous radiotherapy or surgery for brain metastases.
9. Contraindications to radiotherapy for uncontrolled systemic lupus erythematosus, scleroderma, or other connective tissue diseases.
10. Other malignant neoplasms (except non-melanoma skin cancer and cervical cancer) within five years.
11. Any medical or non-medical reason that prevents the patient from continuing to participate in research.
12. It is expected that the patient will not be able to comply with the procedures, restrictions, and requirements of the study and the investigator determines that the patient is unfit to participate in the study.
13. Received studying drugs within 5 half-lives or 3 months, whichever is greater.
14. Currently receiving drugs or herbal supplements known to be potent inducers of Cytochrome P450 3A4(CYP3A4) or unable to be discontinued prior to receiving the first dose of study treatment) (at least 3 weeks prior).
15. The patient is taking any drug known to prolong the QT interval and cannot be discontinued until treatment with amitriptyline.
16. Pregnancy or breastfeeding.