Five-fraction (fr) stereotactic radiosurgery (SRS) is increasingly being applied to large brain metastases (BMs) >2-3 cm in diameter, for which 30-35 Gy is the commonly prescribed dose. Since 2018, to further enhance both safety and efficacy, we have limited the five-fr SRS to approximately ≤3 cm BMs and adopted our own modified dose prescription and distribution: 43 and 31 Gy cover the boundaries of the gross tumor volume (GTV) and 2 mm outside the GTV, respectively, along with a steep dose increase inside the GTV boundary, that is, an intentionally very inhomogeneous GTV dose. Herein, we describe a case of symptomatic BM treated with five-fr SRS using the above policy, which resulted in a maximum tumor response with nearly complete remission (nCR) followed by gradual tumor regrowth despite obvious tumor shrinkage during irradiation.A 71-year-old man who had previously undergone surgery for squamous cell carcinoma (SCC) of the lungs presented with right-sided hemiparesis attributed to the para-falcine BM (27 mm in maximum diameter, 5.38 cm3). The BM was treated with five-fr SRS, with 99.2% of the GTV covered with 43 Gy and 59% isodose. Neurological symptoms improved during SRS, and obvious tumor shrinkage and mitigation of perilesional edema were observed upon completion of SRS. No subsequent anti-cancer pharmacotherapy was administered due to idiopathic pulmonary fibrosis (IPF). Despite a maximum response with nCR at four months, the tiny residual enhancing lesion gradually enlarged from 7.7 months to 22.7 months without neurological worsening. Although a consistent T1/T2 mismatch suggested the dominance of brain radionecrosis,11C-methionine positron emission tomography showed increased uptake in the enhancing lesion. Pathological examination after total lesionectomy at 24.6 months revealed viable tumor tissue. Post-SRS administration of nintedanib for IPF may have provided some anti-tumor efficacy for lung SCC and may mitigate the adverse effects of SRS. The present case suggests that even ≥43 Gy with ≤60% isodose to the GTV boundary and ≥31-35 Gy to the 2 mm outside the GTV are insufficient to achieve long-term local tumor control by five-fr SRS alone in some large BM from lung SCC.